The overall objective of the research is to gain understanding of how fluorinated inhalation anesthetics are biodegraded so that the risk of fluoride nephropathy following anesthetic administration may be reduced. During the first year of the project we found that 1) sevoflurane (fluoro-methyl-1,1,1,3,3,3-hexafluoro-isopropyl ether) was not nephrotoxic in enzyme induced animals; 2) that phenytoin (Dilantin) is qualitatively and quantitatively similar to phenobarbital with regard to induction of anesthetic metabolism and exacerbation of methoxyflurane nephrotoxicity and 3) that the rate limiting step in methoxyflurane defluorination is different in hepatic microsomes prepared from enzyme induced animals as compared to microsomes from control animals. Studies in progress are investigating 1) the effect of ethanol on anesthetic metabolism; 2) the kinetics of anesthetic metabolism in vitro and in vivo and 3) manner in which the mechanism of methoxyflurane defluorination changes with enzyme induction. BIBLIOGRAPHIC REFERENCES: Hitt BA, Mazze RI, Cook TL, Beppu WJ, Kosek JC: Thermoregulatory defect during anesthesia. Anesth and Analg 56:1-7, 1977. Mazze, R.I.: Methoxyflurane nephrotoxicity. Environmental Health Perspectives. 15:111-119, 1976.